Thymic involution and proliferative T-cell responses in multiple sclerosis

Duszczyszyn, Danielle A.; Williams, Julia L.; Mason, Helen; Lapierre, Yves; Antel, Jack; Haegert, David G.

doi:10.1016/j.jneuroim.2010.02.005

« Previous Next »Journal of Neuroimmunology
Volume 221, Issue 1 , Pages 73-80, 15 April 2010

Thymic involution and proliferative T-cell responses in multiple sclerosis

Danielle A. Duszczyszyn
- Department of Pathology, McGill University, Duff Medical Building, 3775 rue University, Montreal, Quebec, Canada H3A 2B4
- D. A. D., J. L. W., and D.G. H. contributed equally.
Julia L. Williams
- Department of Pathology, McGill University, Duff Medical Building, 3775 rue University, Montreal, Quebec, Canada H3A 2B4
- D. A. D., J. L. W., and D.G. H. contributed equally.
Helen Mason
- Department of Pathology, McGill University, Duff Medical Building, 3775 rue University, Montreal, Quebec, Canada H3A 2B4
Yves Lapierre
- Department of Neurology, McGill University, 3601 rue University, Montreal, Quebec, Canada H3A 2B4
Jack Antel
- Department of Neurology, McGill University, 3601 rue University, Montreal, Quebec, Canada H3A 2B4
David G. Haegert
- Department of Pathology, McGill University, Duff Medical Building, 3775 rue University, Montreal, Quebec, Canada H3A 2B4
- Corresponding author. Tel.: +1 514 398 5599; fax: +1 514 398 3465.
- D. A. D., J. L. W., and D.G. H. contributed equally.

Received 27 September 2009; received in revised form 8 January 2010; accepted 8 February 2010. published online 11 March 2010.

Abstract

We investigated naïve CD4 T-cell homeostasis in relapsing–remitting multiple sclerosis (RRMS). Quantification of signal joint T-cell receptor excision circles in FACS-isolated CD31hi cells, which correspond closely to CD4 recent thymic emigrants (RTEs), indicates that young patients have reduced generation of CD4 RTEs compared to age-matched controls. In RRMS, compared to controls, CXCR4 analyses indicate age-associated thymic output of progressively immature CD4 RTEs, and Ki-67 data demonstrate altered T-cell proliferative responses that fail to maintain naïve CD4 T-cell numbers with age. Thus, RRMS patients have early thymic involution with compensatory homeostatic peripheral T-cell proliferative responses that may predispose patients to autoreactivity.

Abbreviations: MS, multiple sclerosis, RRMS, relapsing–remitting MS, TREC, TCR excision circle, sjTREC, signal joint TREC, RTE, recent thymic emigrant, MFI, mean fluorescence intensity